Under certain circumstances heparin stimulates platelets and may cause thrombocytopenia. This laboratory has analyzed the initial step in this process, the binding of heparin to the cells. It has been shown that this binding is saturable and reversible. The binding constants are a function of heparin molecular weight and the state of platelet activation. Activated platelets compete with secreted heparin-binding protein (e.g., platelet factor 4) for heparin.